Chitin and chitosan represent a family of biopolymers, made up of N-acetyl-D-glucosamine and D-glucosamine subunits. Chitin can be found widely in the exoskeletons of arthropods, shells of crustaceans, and the cuticles of insects. Chitosan, although occurring in some fungi, is produced industrially by alkaline hydrolysis of chitin. Their different solubilities in dilute acids are commonly used to distinguish between both polysaccharides. Chitosan, the soluble form, can have a degree of acetylation between 0% and about 60%, the upper limit depending on parameters such as processing conditions, molar mass, and solvent characteristics.
Both chitin and chitosan are promising polymers for a variety of applications, including water treatment (metal removal, flocculant/coagulant, filtration), pulp and paper (surface treatment, photographic paper, copy paper), cosmetics (make-up powder, nail polish, moisturizers, fixtures, bath lotion, face, hand and body creams, toothpaste, foam enhancing), biotechnology (enzyme immobilization, protein separation, chromatography, cell recovery, cell immobilization, glucose electrode), agriculture (seed coating, leaf coating, hydroponic/fertilizer, controlled agrochemical release), food (removal of dyes, solids and acids, preservatives, color stabilization, animal feed additive), and membranes (reverse osmosis, permeability control, solvent separation). Of particular interest are biomedical applications of chitin and chitosan because of their biocompatibility, biodegradability and structural similarity to the glycosaminoglycans. Applications and potential applications include dressings for wound-healing, tissue engineering applications, artificial kidney membranes, drug delivery systems, absorbable sutures, hemostats, antimicrobial applications, as well as applications in dentistry, orthopedics, ophthalmology, and plastic surgery. For comprehensive reviews of potential applications of chitin and chitosan see, for example, [Applications of chitin and chitosan, 1997. Shigemasa and Minami, Biotech Genetic Eng Rev 1996; 13:383-420. Ravi Kumar, React Funct Polym 2000; 46:1-27. Singh and Ray, J Macromol Sci 2000; C40:69-83].
However, despite a great variety of potential applications of chitin and chitosan, only a few products are actually in commercial use. One of the major limiting factors for a still broader utilization is the limited capability for extruding these polysaccharides in an efficient manner to products having the desired properties. As an example, chitin and chitosan fibers are usually made by wet-spinning processes, which produce fibers by first dissolving the polymer in a solvent and then extruding the polymer solution into a nonsolvent. However, chitin is insoluble in common solvents, which prevents facile processing. For example, surgical suture made of chitin fiber has been described in U.S. Pat. No. 3,988,411 to Capozza and U.S. Pat. No. 4,932,404 to Kifune et al. which is fabricated by wet-spinning processes using toxic, corrosive, and expensive halogenated solvents. N,N-dimethylacetamide containing lithium chloride has been shown to be an effective alternative solvent system for chitin, overcoming some of the issues associated with halogenated solvents. For example, as described in U.S. Pat. No. 4,059,457 to Austin, chitin fibers can be fabricated using this solvent system by extrusion into an acetone coagulation bath. However, a general problem remains with the removal of the lithium chloride from the fiber. The lithium acts as a Lewis acid solvating the chitin amide group, and it is unclear if this can be completely reversed through washing, once the fiber has been formed. These issues as well as general aspects of chitin fiber processing and solvent systems have been reviewed thoroughly [Rathke and Hudson, J Mater Sci 1994; C34:375437. Agboh and Qin, Polym Adv Tech 1997; 8:355-365. Ravi Kumar, React Funct Polym 2000; 46: 1-27].
Chitosan is more readily soluble, and fibers can be prepared by extrusion of diluted acidic solutions of chitosan into an alkaline coagulation bath, such as described in U.S. Pat. No. 2,040,880 to Rigby. However, chitosan fibers fabricated in this manner have low mechanical strength in physiological environment, requiring a subsequent covalent cross-linking procedure [Knaul et al., J Polym Sci 1999; B37:1079-1094]. Methods to improve the mechanical strength of chitosan articles, such as fibers and tubes, have also been suggested in U.S. Pat. No. 6,368,356 to Zhong et al., by using a combined ionic and covalent cross-linking process. However, covalent cross-linking regularly involves toxic chemical substances and by-products which may be difficult to remove from the product. Cross-linking also alters the natural chemical structure of the biopolymer, thereby affecting natural biodegradation processes and products. Additionally, the mechanical strength of ionically and/or covalently cross-linked chitosan is still poor under physiological conditions, and articles having a memorized shape such as those described in '356 quickly loose their shape under physiological conditions.
In “Study of a chitin-based gel as injectable material in periodontal surgery”, Biomaterials 2002; 23:1295-1302, Gérentes et al. disclose a treatment of periodontal disease by means of injecting a mixture containing chitosan and acetic anhydride before gelation. In “Chitin-based tubes for tissue engineering in the nervous system”, Biomaterials 2005; 26:4624-4632, Freier et al. disclose a method of manufacturing tubes by means of injecting a mixture containing chitosan and acetic anhydride into a mold before gelation.
By considering the aforementioned limitations in the prior art it would be advantageous to manufacture chitin/chitosan-based fibers, tubes and other articles by a simple, inexpensive and efficient process, without the use of toxic solvents and cross-linking agents, and without the release of toxic by-products. It would further be advantageous to manufacture chitin/chitosan-based fibers, tubes and other articles by an extrusion process, leading to sufficient mechanical strength of the extruded products under physiological conditions. It would further be advantageous to manufacture chitin/chitosan-based shaped articles which have an improved mechanical stability under physiological conditions, including a mechanically stable shape-memory which allows the article to be reversibly shaped in different conformations. It would further be advantageous to manufacture chitin/chitosan-based shaped articles which allow for controlled degradation and/or dissolution to non-toxic products under physiological conditions. These and other needs are met in the present invention.